Tumors arising from non-neural or glial tissue of the brain ('gliomas') constitute one of the most lethal human cancers. Few case-control studies of glioma have been undertaken, and the etiology of the tumor is largely unknown. However, the descriptive epidemiology of the disease, including an unexplained excess of glioma n the southeastern US, is consistent with an environmental component in the disease. Strong candidate risk factors, based on experimental evidence, include exposure to N-nitroso compounds (NOCs) in processed meats, and tobacco products, and consumption of alcohol. To shed light on the contribution of diet, genes and other potential risk factors to adult glioma, we are proposing a clinic-based, multi-institutional case- control study. Adults with a new diagnosis of glioma will be recruited from 5 treatment referral centers in the southeastern US. Subjects will be enrolled directly from clinics, generally within days or weeks of diagnosis. In the 5-year project, an estimated 1,200 persons with incident glioma and age- and gender-matched community controls will be enrolled in the study. Information on diet will be collected using a validated food frequency questionnaire, supplemented with a questionnaire developed by Sinha and colleagues at NCI designed specifically to measure NOCs and other meat carcinogens in the diet. In a structured interview, data will also be gathered on atopic immunity, and other exposures linked in past studies to glioma risk. To explore the contribution of genetic susceptibility, oral DNA samples will be collected from cases and controls, and whole genome amplification undertaken to augment the DNA for planned and future genotyping. Both candidate SNPs and haplotypes will be examined in a set of 31 proposed susceptibility genes involved in NOC metabolism, DNA repair and access of carcinogens to the CNS. With the large numbers available for analysis, the study will have power to investigate interactions of alcohol consumption and NOC exposure with the susceptibility genes in these pathways. The proposed study will be the largest US case-control study of glioma. Based in a high incidence region, the study may identify novel environmental risk factors and offer new insights on prevention and treatment for a leading fatal cancer in the US.